Clinical Manifestations Of Antiphospholipid Syndrome Research Articles

Antiphospholipid Syndrome: Endocrinologic Manifestations and Organ Involvement

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic tendency that affects most organ systems in the human body. In this report, we present a review of the endocrinologic manifestations associated with APS by evaluating the medical literature from 1968 to 2009 using MEDLINE and these keywords: APS, antiphospholipid syndrome, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, anti β-2 glycoprotein I, pituitary, adrenal, thyroid, parathyroid, ovary, testes, diabetes mellitus, and diabetes insipidus. Adrenal insufficiency was found to be the most common endocrine manifestation associated with APS. Autoimmune thyroid disease was associated with increased titers of antiphospholipid antibodies (aPL) without any APS clinical manifestations. In addition, hypopituitarism and Sheehan syndrome are increasingly being reported in association with aPL. Data regarding the prevalence and significance of aPL in diabetic patients remains uncertain. Finally, only a few cases of ovarian and testicular derangements have been reported. APS should be considered in any patient with adrenal insufficiency even in the absence of other thrombotic manifestations. It is also advisable to assess aPL in the sera of patients presenting with pituitary insufficiency. Further studies are needed to clarify the relationship between aPL and thyroid disorders and diabetes mellitus.

Risky business: the interpretation, use, and abuse of antiphospholipid antibody tests in clinical practice

Antiphospholipid antibodies (aPL) are best considered as risk factors. aPL are not diagnostic tests and considering them as such can be misleading and may direct attention away from the more important clinical issue of risk modification and management. When considering aPL as risk factors, quantitative aPL tests such enzyme-linked immunosorbent assay (ELISA) for anticardiolipin (aCL) and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies, should be interpreted carefully. Risk for clinical manifestations appears to be associated with moderate to high levels of these autoantibodies. Lower levels may be statistically abnormal compared with a control population, but may not be associated with the risk of thrombosis or pregnancy loss. Lupus anticoagulants (LA) are generally thought to be more strongly associated with the risk of clinical manifestation of antiphospholipid syndrome (APS) than aCL and anti-beta(2)GPI antibodies. One reason for the stronger association may be related to patients' antibody titers. LA assays are not very analytically sensitive, i.e. a relatively high concentration of antibodies is required to prolong the clotting time in these tests. Thus, the presence of LA indicates a high titer of aPL and this, rather than the intrinsic functional characteristics of LA antibodies, may explain the high risk of clinical manifestations associated with LA.

Antiphospholipid antibodies in critical illness

The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapies are the mainstay of treatment to reduce the risk of recurrent thromboembolism. Among patients with antiphospholipid antibodies, the absolute risk of new thrombosis developing is low in healthy patients without previous thrombotic events. However, the risk of recurrent thrombosis appears to be high in patients with a history of arterial or venous thrombosis. Compared with placebo or untreated control, anticoagulation with warfarin administered to achieve an international normalized ratio of 2.0 to 3.0 probably reduces the risk of recurrence of thrombotic events. Aspirin and moderate-intensity warfarin appear equally effective for preventing recurrent stroke in patients with a single positive antiphospholipid antibody test result and previous stroke. It is unknown how best to prevent first stroke in patients found to be persistently positive for the antiphospholipid syndrome. The catastrophic variant of the antiphospholipid syndrome is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time. This condition has a very high mortality rate. First-line treatment with therapeutic anticoagulation, corticosteroids, plasma exchange, and intravenous immunoglobulin seems to be effective in reducing mortality and risk of catastrophic thrombotic events in these patients. In conclusion, moderate-intensity warfarin is effective for preventing recurrent thrombotic events in patients with venous thrombosis. Aspirin appears to be as effective as moderate-intensity warfarin for preventing recurrent stroke in patients with previous stroke and a single positive test result for antiphospholipid antibody. The optimal treatment of other clinical manifestations of antiphospholipid syndrome needs to be addressed in well-designed prospective studies.

Ocular disorders as the prevailing manifestations of antiphospholipid syndrome: a case series

IntroductionAntiphospholipid syndrome is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The systemic features of the syndrome are characterized by large variability depending on the affected organ(s). Among them, neurological and behavioural disturbances, dermatological features as livedo reticularis and renal, ocular, liver or valvular heart manifestations have been reported in antiphospholipid syndrome patients. However, studies on the frequency and clinical presentation of the ocular manifestations as the prevailing (first) sign of antiphospholipid syndrome in patients suffering from "unexplained" ocular disease are missing. Herein, we present three cases suffering from unexplained ocular disease as first manifestation of antiphospholipid syndrome.Case presentationAll the three patients were referred to our department because of unexplained ocular features from the anterior or posterior segment and unexplained neuro-ophthalmologic symptoms. The first patient had bilateral retinal occlusive disease, the second and the third patient had unilateral nonarteritic anterior ischemic optic neuropathy with macular oedema. Moderate to high levels of antiphospholipid antibodies were detected in all of them at baseline as well as 6 to 12 weeks after initial testing confirming the presence of antiphospholipid antibodies. Anticoagulant treatment with acenocoumarol was instituted resulting in stabilization and/or improvement of ocular signs in all of them.ConclusionDue to the important diagnostic and therapeutic implications of antiphospholipid syndrome, the possibility of ocular features as the first clinical manifestation of antiphospholipid syndrome should be kept in mind of the physicians particularly in patients with no evident risk factors for ocular disease. In this case, prompt anticoagulant treatment and close follow-up seem to be essential for vision salvation and stabilization.

Prevalence of Anticardiolipin Antibodies in Patient Cohorts with Distinct Clinical Manifestations of the Antiphospholipid Syndrome

Clinical manifestations of antiphospholipid syndrome (APS) vary from venous and arterial thrombosis to pregnancy loss and pre-eclampsia (PEC). Our aims were to establish the prevalence of anticardiolipin antibodies (aCLA) in patients with clinical features of APS and to compare the reference ELISA method with the novel automated EliA aCLA assay. Serum samples from 1278 patients with either deep venous thrombosis (DVT), young stroke (YS), PEC, or multiple sclerosis (MS) were included. The latter cohort was included because initial presentation of APS might resemble MS. Using the internationally accepted cutoff level of 40 MPL/GPL [IgM antiphospholipid units/mL (MPL)/IgG antiphospholipid units/mL (GPL)], 0.7% and 0.5% of the samples were positive for IgM and IgG aCLA by ELISA, respectively. Using the cutoff level recommended by the manufacturer (15 MPL/GPL), the prevalence was 2.7% and 2.8%, respectively. The prevalence by EliA was 2.0% and 0.5% for IgM and IgG aCLA, respectively (40 MPL/GPL cutoff). However, with a low cutoff level, the prevalence of IgM aCLA, but not IgG aCLA, was higher in the DVT (14.3%), YS (14.6%), and PEC (17.7%) cohorts but not the MS cohort. The prevalence of aCLA was too low for reliable determination of concordance between assays. In patients with DVT, CVA, PEC, and MS, the prevalence of aCLA is low, in particular when internationally accepted cutoff values are applied. Our finding questions the efficacy of aCLA testing. Therefore, there might be either a need for defining specific clinical criteria to obtain a better rational for aCLA testing or aCLA testing should be excluded from the classification criteria.

STAT4 single nucleotide polymorphism, rs7574865 G/T, as a risk for antiphospholipid syndrome

Genetic factors are hypothesised to play a role in the susceptibility to antiphospholipid syndrome (APS) based on several family studies in patients with anti-phospholipid antibodies (aPL) and/or clinical manifestations of...

P65 A variety of clinical manifestations of antiphospholipid syndrome in obstetric practice

P65 A variety of clinical manifestations of antiphospholipid syndrome in obstetric practice

Atypical clinical manifestation of antiphospholipid syndrome

Antiphospholipid syndrome is a disorder characterized by recurrent venous or arterial thrombosis and/or recurrent abortions associated with persistently elevated levels of antiphospholipid antibodies. In some patients antiphospholipid syndrome occurs in association with systemic lupus erythematosus, or other autoimmune disorders or malignancies. Antiphospholipid syndrome can be induced by certain drugs. A correct diagnosis of this disease is necessary as it is potentially associated with serious and sometimes life-threatening complications. Clinical presentations of antiphospholipid syndrome may vary widely even in the same patient. The time between individual manifestations of the disease also varies considerably. Therefore its early detection requires a strong index of suspicion especially when thrombosis occurs at unusual sites or non-specific symptoms predominate in the clinical presentation. We report a case of a 20-year-old woman with a recent history of pulmonary embolism who was admitted to the hospital because of severe symptomatic anemia. Once the diagnosis of antiphospholipid syndrome coexisting with systemic lupus erythematosus as a primary disorder has been established, implemention of specific treatment resulted in markedly improved condition.

Antiphospholipid antibodies in Brazilian hepatitis C virus carriers

Hepatitis C, a worldwide viral infection, is an important health problem in Brazil. The virus causes chronic infection, provoking B lymphocyte dysfunction, as represented by cryoglobulinemia, non-organ-specific autoantibody production, and non-Hodgkin's lymphoma. The aim of this research was to screen for the presence of antiphospholipid autoantibodies in 109 Brazilian hepatitis C virus carriers without clinical history of antiphospholipid syndrome. Forty healthy individuals were used as the control group. IgA, IgG, and IgM antibodies against cardiolipin and ss2-glycoprotein I were measured with an enzyme-linked immunosorbent assay, using a cut-off point of either 20 UPL or 20 SBU. While 24 (22.0%) hepatitis C carriers had moderate titers of IgM anticardiolipin antibodies (median, 22.5 MPL; 95%CI: 21.5-25.4 MPL), only three carriers (<3%) had IgG anticardiolipin antibodies (median, 23 GPL; 95%CI: 20.5-25.5 GPL). Furthermore, IgA anticardiolipin antibodies were not detected in these individuals. Male gender and IgM anticardiolipin seropositivity were associated in the hepatitis C group (P = 0.0004). IgA anti-ss2-glycoprotein-I antibodies were detected in 29 of 109 (27.0%) hepatitis C carriers (median, 41 SAU; 95%CI: 52.7-103.9 SAU). Twenty patients (18.0%) had IgM anti-ss2-glycoprotein I antibodies (median, 27.6 SMU; 95%CI: 23.3-70.3 SMU), while two patients had IgG antibodies against this protein (titers, 33 and 78 SGU). Antiphospholipid antibodies were detected in only one healthy individual, who was seropositive for IgM anticardiolipin. We concluded that Brazilian individuals chronically infected with hepatitis C virus present a significant production of antiphospholipid antibodies, mainly IgA anti-ss2-glycoprotein I antibodies, which are not associated with clinical manifestations of antiphospholipid syndrome.

Antiphospholipid antibodies in HIV-positive patients

Antiphospholipid (aPL) antibodies classically have been associated with thrombotic phenomena and abortion in patients with autoimmune diseases. The objective of the present work was to evaluate the frequency of such antibodies in patients infected with HIV and study its association with the presence of clinical manifestations of antiphospholipid syndrome (APS). Using a transversal study, a population of patients diagnosed with HIV, identified through an enzyme-linked immunosorbent assay (ELISA) test and confirmed by Western blotting, aged above 17 years old, was investigated. Through a standard questionnaire, the presence of APS manifestations was investigated, as well as the frequency of rheumatic manifestations. Antibodies against beta2 glycoprotein I (anti-beta2 GPI) and anticardiolipin (aCL) IgA, IgG, and IgM were investigated by the ELISA method using commercial kits (QUANTA Lite, INOVA Diagnostics). Ninety patients were studied, 47 (52.2%) male and 43 (47.8%) female. Clinical manifestations of APS were detected in 12 patients (13.3%) of the studied population, whereas arthralgia was the most common rheumatic manifestation (38.9%). Of the 90 patients, 40 (44.4%) were reactive for at least one type of aPL antibody (aCL and/or anti-beta2 GPI). The frequency of aCL was 17.8%, from which 15 (16.7%) had aCL IgG, 3 (3.3%) IgM, and 1 (1.1%) IgA. The frequency of the anti-beta2 GPI antibody was 33.3%, from which 29 (32.2%) were positive for isotype IgA, 4 (4.4%) isotype IgM, and 1 (1.1%) isotype IgG. No association was observed between immunoreactivity for aPL antibodies in general or each isotype in particular and the presence of APS manifestation. In the present study, it was possible to observe a relatively high frequency of aPL antibodies, particularly for isotype IgA anti-beta2 GPI in HIV. However, there was no association to APS manifestations, suggesting that such antibodies had no etiopathogenic role in these complications in patients with such retroviral infection.

Endocrinologic Manifestations of the Antiphospholipid Syndrome

Our objective was to study the endocrinologic manifestations of the antiphospholipid syndrome (APS). We reviewed the medical literature from 1968 until 2005 using MEDLINE and the key words: APS, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid antibodies, adrenal, thyroid, parathyroid, pituitary, diabetes, ovaries and testes. Adrenal insufficiency is the most common endocrinologic manifestation and can be the presenting symptom of APS. In patients with autoimmune thyroid disease circulating aPL have been detected. However, no clinical manifestations of APS have been described. A few cases of hypopituitarism have been reported, including a case of Sheehan's syndrome. aPL has been detected in the sera of diabetic patients, probably associated with some macroangiopathic complications. Finally only very few cases of ovarian and testicular involvement have been reported. The adrenals are the most commonly involved glands in the APS. Clinicians should keep a high index of suspicion for adrenal insufficiency in patients with APS.

Sudden sensorineural hearing loss in a patient with primary antiphospholipid syndrome

An autoimmune basis for sudden sensorineural hearing loss (SSNHL) has long been suspected. Immunoserological assays of patients with SSNHL have revealed the presence of different antibodies. Recently a number of case reports have highlighted the association of anticardiolipin antibodies (aCA) and SSNHL in systemic lupus erythematosus (SLE) [1]. Here we report a case with primary antiphospholipid syndrome (APS) who had SSNHL. A twenty eight years old male patient was applied to our hospital with the complaint of bilateral, sudden onset deafness. Past medical history revealed that he had Wernicke aphasia lasted one hour one year ago. Systemic and neurologic examinations were normal except bilateral sensorineural hearing loss. Complete blood count, PT, aPPT, sedimentation, biochemistry, protein C, S antithrombin III and complement levels were in normal limits. ECG and echocardiogram were normal. We confirmed bilateral sensorineural hearing loss with audiogram. Cranial and temporal bone MRI were normal. Anti HIV and VDRL were negative. Anticardiolipin antibody Ig G was positive (28 IU/mL). In repeated tests, ANA, anti-DNA and aCA IgM were found negative, but aCA Ig G was positive. Prednisone 80 mg/day was started and continued with decreasing doses for 3 months. He has completely recovered in one month. Then he was anticoagulated. No other ischemic attack, any systemic finding or audiovestibular complaint have been seen for two years. APS occurs in isolation (primary APS) or in association with connective tissue diseases (secondary APS), particularly with SLE [2]. The most common clinical manifestation of APS is thrombosis, which affects the vessels of any organ. Arterial thrombosis involves the brain in up to 50% of cases, causing transient ischemic attack or stroke [3]. Other neurological mani-

Prevalence of Antiphospholipid and Antioxidized Low-Density Lipoprotein Antibodies in Rheumatoid Arthritis

Antiphospholipid antibodies characterize the antiphospholipid syndrome (APS), but they can also be found in various autoimmune, infectious, and malignant conditions. This study's objectives were to detect the prevalence of antiphospholipid and antioxidized low-density lipoprotein (anti-oxLDL) antibodies among patients with rheumatoid arthritis (RA) who did not have clinical manifestations of APS. Using a standard enzyme-linked immunosorbent assay (ELISA), we evaluated the levels of immunoglobulin G (IgG) and IgM anticardiolipin, IgG, and IgM anti-beta-2-glycoprotein-I (anti-beta(2)GPI), and anti-oxLDL autoantibodies in 82 patients with RA. The cutoff levels for detecting these autoantibodies were 15 IgG phospholipid units (GPL), 15 IgM phospholipid units (MPL), and 25 ELISA units (EU)/mL, respectively. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 10 with low levels of IgG anticardiolipin and 7 with medium to high levels of anticardiolipin autoantibodies. IgM anticardiolipin was found in only 1 (1%) patient, and both IgG and IgM anti-beta(2)GPI were found in 3 (4%) patients with RA. Elevated levels of anti-oxLDL antibodies were found in 8 (10%) patients, 4 of whom also had elevated levels of IgG anticardiolipin. We conclude that IgG anticardiolipin autoantibodies can be found in about one-fifth of RA patients who do not have clinical manifestations of APS. Whether the presence of anticardiolipin signifies increased risk for thrombosis and atherosclerosis in these patients should be studied further.

Apolipoprotein H (apoH)-dependent autoantibodies and apoH protein polymorphism in selected patients showing lupus anticoagulant activity

Apolipoprotein H (apoH) is considered to be a necessary cofactor for the binding of certain antiphospholipid antibodies to anionic phospholipids. Some apoH-dependent antiphospholipid antibodies also exert lupus anticoagulant (LA) activity, which seems to depend on antiphospholipid antibody epitope specificity. The aim of this study was to evaluate whether the presence of less frequent apoH alleles may induce structural or conformational changes in these "LA-dependent" regions that may initiate more frequent autoimmune responses in subjects. We selected patients with confirmed LA activity and none or low titers of anticardiolipin antibodies that had been sent to the laboratory for routine antiphospholipid antibody determination. Many of them had some clinical manifestation of antiphospholipid syndrome. Antibodies to apoH were determined with a commercially available anticardiolipin/apoH ELISA kit. ApoH protein polymorphism (apoH phenotype) was demonstrated by isoelectric focusing and immunoblotting. Our results showed that 47/74 (63.5%) of our selected LA-positive patients also had elevated apoH-dependent antiphospholipid antibody titers. These results point to two subgroups of patients according to the LA potency of apoH-dependent antibodies. A strong positive correlation (non-linear or linear) for apoH-dependent antibody titers and LA activity was observed in both subgroups of patients. In this study, we did not find significant differences in the distribution of apoH phenotypes among control subjects and patients with apoH-dependent/LA-positive auto- antibodies.

The antiphospholipid antibody syndrome: diagnostic aspects

The antiphospholipid antibody syndrome is an important cause of arterial and/or venous thrombosis. In this review the authors discuss recent trends in the clinical and laboratory diagnosis of this syndrome that are of relevance to ophthalmologists. The diagnostic criteria of antiphospholipid antibody syndrome have been reviewed and revalidated recently. Few prospective studies have been conducted to determine the prevalence of antiphospholipid antibodies in patients with retinal vascular occlusion and the spectrum of ophthalmologic findings in patients with established antiphospholipid syndrome. New antibody tests for antiphospholipid antibody syndrome are available with increased sensitivity and specificity, but lack of standardization, and interassay and interlaboratory variation makes it difficult to determine their clinical value. Ophthalmologists should be familiar with the spectrum of clinical manifestation of antiphospholipid syndrome, the diagnostic criteria of this disease, and be able to carry out a basic laboratory workup for this entity. A high index of suspicion for this disorder is also important in making the diagnosis.

Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death

AbstractThe antiphospholipid syndrome (APS) is associated with thrombosis and fetal death but the pathologic mechanisms are poorly understood. Since endothelial protein C receptor (EPCR) plays a role in the anticoagulant system and in placental development, we hypothesized that anti-EPCR autoantibodies may be involved in clinical manifestations of APS and in fetal loss. The levels of immunoglobulin M (IgM) and IgG anti-EPCR autoantibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) in 43 patients with APS and 43 controls. Anti-EPCR levels were higher in APS patients than in controls. Interestingly, one of the IgM anti-EPCR autoantibodies inhibited the generation of activated protein C on endothelium. Since markedly high anti-EPCR levels were found in women with fetal death, 87 patients with a first episode of unexplained fetal death were subsequently analyzed and their anti-EPCR levels were compared with 87 matched controls. We found that anti-EPCR autoantibodies constitute an independent risk factor for a first fetal death episode: the adjusted odds ratios (ORs) for anti-EPCR autoantibodies above the 95th percentile were 23.0 (95% confidence interval [CI], 2.0-266.3) for IgM and 6.8 (95% CI, 1.2-38.4) for IgG. Anti-EPCR autoantibodies can be detected in APS patients and are independent risk factors for fetal death.

Antiphospholipid syndrome in Asians: clinical manifestations, serological markers and outcome of the National University of Singapore/National University Hospital antiphospholipid cohort

AbstractBackground: There is a paucity of studies on antiphospholipid syndrome (APS) in Asian patients.Aim: This is the first study in Singapore to describe the clinical features, serological markers and outcomes of one of the largest cohort of APS patients in South‐east Asia.Method: One hundred and forty‐six patients were studied.Results: Within the study group, 89 were primary APS and 57 secondary APS. Age range: 16–84 years (mean Age: 50.1 years). Male : female ratio: 1 : 2.1. Racial distribution: Chinese, 69.2%; Malays, 18.5%; Indians, 11.7%. Systemic lupus erythematosus was the commonest disease associated in 48 patients (32.9%), while 17 (11.6%) had lupus‐like disease. Eighty‐two (56.2%) patients had arterial thrombosis, 37 (25.3%) patients had venous thrombosis, 14 (9.6%) had arterial and venous thrombosis while 17 (11.6%) had obstetric manifestations; 28.8% had thrombocytopenia. Clinical manifestations were diverse with neurological (49.3%), cardiac (40%), renal (23.6%) involvement. There were also several unusual presentations. Recurrent thrombosis occurred in 24.6%. Two had catastrophic APS and there were 12 deaths (9.6%). Antiphospholipid antibody testing included lupus anticoagulant, serum aCL IgG, IgM and IgA, anti‐β2 glycoprotein I (aβ2‐GPI) IgG, IgM, and IgA. The serological positivity rates of the various antiphospholipid antibodies were reported. aβ2‐GPI was positive in 67% of those tested, of which aβ2‐GPI IgA was the most common subtype. The presence of the aβ2‐GPI was associated with recurrent venous thrombosis.Conclusion: The clinical manifestations of APS in Asian patients were diverse and multisystemic. Recurrent thrombosis rate was high with significant morbidity and mortality.

Antiphospholipid syndrome in obstetrics.

Antiphospholipid syndrome (APLS) in pregnancy is characterized by the presence of autoantibodies in association with recurrent fetal loss and severe complications such as preeclampsia, fetal growth retardation, or placental insufficiency. The most clinically important serologic markers are lupus anticoagulant, anticardiolipin antibodies, and recently anti-beta-2-glycoprotein 1 antibodies. At present, standardization does not exist and a definitive association between specific clinical manifestation and antibody level is not yet known. Experimental data gave evidence that passive transfer of antiphospholipid antibodies result in clinical manifestation of APLS, that is, fetal loss and thrombocytopenia. Treatment with heparin, aspirin, or intravenous immunoglobulins decreased the fetal loss rate. Treatment regimens in human are very difficult to interpret. Evidence from two prospective studies supported treatment with heparin and aspirin to improve pregnancy outcome. The risk of preeclampsia and placental insufficiency was substantial and occurred in 50% of patients. The general failure rate of heparin/aspirin treatment is approximately 30%. In such cases intravenous immunoglobulin in combination with heparin and aspirin has been used to treat APLS.

Valine/valine genotype at position 247 of the beta2-glycoprotein I gene in Mexican patients with primary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies.

To determine the polymorphism at position 247 of the beta(2)-glycoprotein I (beta(2)GPI) gene in Mexican patients with antiphospholipid syndrome (APS) and to compare these data in patients with or without antibodies to beta(2)GPI and with the clinical manifestations of APS. We studied 39 patients with primary APS and compared them with 106 clinically healthy subjects. Polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. The presence of "true" anticardiolipin (aCL) antibodies, beta(2)GPI-dependent aCL antibodies (IgG and IgM), and phospholipid-free anti-beta(2)GPI antibodies (IgG isotype) were detected by enzyme-linked immunosorbent assay (ELISA) utilizing nonirradiated ELISA plates. Clinical manifestations associated with antiphospholipid antibodies were also evaluated. We found no significant differences in the genotype expression between the control group and the primary APS patients (13% with VV, 52% with VL, and 35% with LL versus 23% with VV, 51% with VL, and 26% with LL, respectively). In contrast, anti-beta(2)GPI-positive patients had significantly higher frequencies of the VV genotype and V allele expression than the control subjects and the anti-beta(2)GPI-negative patients. These genotype and allele frequencies were also significantly higher in patients with arterial thrombosis than in patients without it. Anti-beta(2)GPI-negative patients without arterial thrombosis did not express the VV genotype. We found no differences in the Val/Leu(247) polymorphism of the beta(2)GPI gene in primary APS patients with or without "true" aCL antibodies or in primary APS patients with or without beta(2)GPI-dependent aCL antibodies. Our results suggest that the VV genotype at position 247 of the beta(2)GPI gene may play a role in the generation of anti-beta(2)GPI antibodies and perhaps in the expression of arterial thrombosis in primary APS.

Caractéristiques cliniques et sérologiques du lupus érythémateux systémique : à propos de 128 cas

Objective – To analyse the clinical and serological characteristics of systemic lupus erythematosus (SLE) in the center of Tunisia.Methods – We studied 128 patients with SLE aged one to 73 years. Antinuclear antibodies (ANA) were detected by an immunofluorescence method. Anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen antibodies (anti-Sm, anti-SS-A, anti-SS-B and anti-RNP) and anti-cardiolipin (aCL of IgG, IgA and IgM isotypes) antibodies were detected by ELISA.Results – Malar rsah (71%) and anemia (71%) were the most commun clinical manifestations. Arthritis was seen in 62.5%. Severe kidney damage was observed in 39%. Pericarditis and pleuritis were observed in only 23%. Neurological manifestations (16%) were uncommun. Clinical manifestations of anti-phospholipid syndrome (SAPL) were observed in 15%. ANA were detected in 100%, anti-dsDNA in 76%, anti-Sm in 55.5%, anti-SS-A in 64%, anti-SS-B in 33.6%, anti-RNP in 49%. aCL of IgG, IgA and IgM isotypes were detected in 63.5%, 49% and 40.6% of the patients respectively. The only significant positive clinical associations were those of arthritis with anti-dsDNA antibodies (p=0.022) and malar rash with anti-SS-A antibodies (p=0.002).Conclusions – This study suggests that tunisians with SLE present, in general, a mild form of disease predominantly manifested by cutaneous, musculoskeletal and hematologic involvement but low prevalence of major organ damage.